In order to understand the molecular mechanism by which Herpes viruses transform normal human cells to their malignant state we have attempted to identify and characterize the viral gene sequences in human lymphoblastoid cell lines and in leukocytes from patients with leukemia and lymphomas. We have cloned specific viral DNA sequences in E. coli and have used these DNA sequences as probes to search for complementary DNA in various lymphoblastoid cells. A cloned DNA sequence encompassing the viral thymidine kinase gene appears to be present in certain lymphoblastoid cells. Current experiments are in progress to transcribe and translate the cloned viral DNA in vitro, characterize the protein products and analyze if these proteins are present in lymphoblastoid cells and related tissues from patients with various leukemias and lymphomas. We have also discovered a new topoisomerase that copurified with the DNA polymerase induced by herpes simplex virus. The role of the viral topoisomerase to catenate and decatenate the replicative intermediates of the viral DNA is now being analyzed.